Is There Any Scientific Basis of Hawan to be used

in Epilepsy-Prevention/Cure?
Review
Journal of Epilepsy Research
pISSN 2233-6249 / eISSN 2233-6257
1 1 1 2 1
Parveen Bansal , Ramandeep Kaur , Vikas Gupta , Sanjiv Kumar , RamanPreet Kaur
1
Baba Farid University of Health Sciences University Centre of Excellence in Research; 2National Medicinal Plant
Board, Department of AYUSH, Punjab, India

Received August 21, 2015
Accepted October 1, 2015
Corresponding author: Parveen Bansa
Baba Farid University of Health Sciences
University Centre of Excellence in
Research
Tel. 08872016290
Fax. 01639256252
E-mail; ucer_bfuhs@rediffmail.com
Epilepsy is a neuropsychiatric disorder associated with religiosity and spirituality. Nasal drug delivery
systems are the best for diseases related to brain. In older times RishiMuni, ancient scholars and physi-
cians used to recommend Hawan for mental peace and well being. Gayatri Mantra also tells that sugh-
andhim (aroma, fragrance) puushtivardhanam (gives rise to good health). Om triambkum yajamahe,
sughandhim puushtivardhanam, urvarukmev vandhanaat, mrityu mokshay mamritaat! Hawan is a sci-
entific experiment in which special herbs (Hawan Samagri) are offered in the fire of medicinal woods ig-
nited in a specially designed fire pit called agnikuñda. Hawan seems to be designed by the ancient
scholars to fight with the diseases of the brain. Our metadata analysis demonstrates that the compo-
nents of Hawan are having a number of volatile oils that are specifically useful for epilepsy through one
or the other mechanism of action. Due to high temperature of fire the vapors of these oils enter into the
central nervous system through nasal route. The routine of performing Hawan might keep the threshold
value of the therapeutic components in the body and help in preventing epilepsy. In the present manu-
script authors have tried to highlight and integrate the modern and ancient concepts for treatment and
prevention of epilepsy. (2015;5:33-45)
Key words: Epilepsy, Hawan, Traditional therapies, Volatile oil

Introduction
Epilepsy is a neuropsychiatric disorder with high prevalence among
children and young adults. In India, about 10 million people suffer
from epilepsy with a prevalence of about 1.9% in rural areas and
0.6% in urban locales. The greater prevalence of epilepsy in rural
areas is a testament to impact of stigma that surrounds this illness on
levels of treatment that Indians receive. About 95% of people in
India who suffer from epilepsy are never treated for it and almost half
1,2
of sufferers do not have access to anti epileptic drugs. It is the most
3,4
expensive chronic neurological brain disorder in Europe. According
to the World Health Organization and the World Bank, the costs of
5
epilepsy constitute 0.5% of all diseases.
In ancient as well as present times, epilepsy has been associated
6
with religiosity and spirituality. People with epilepsy of comparable
severity may differ widely in quality of life (QOL). A study considered
the possible role of spirituality and it has been reported that spiritu-
7
ality could contribute to QOL in epilepsy. In another study, the com-
plementary and alternative approaches have been successfully dem-
8
onstrated in epilepsy management.
In ancient times this disease was considered as a sacred disease
and a number of superstitious measures used to be taken to pre-
vent/cure it. Yajurveda advocates performing of Hawan every day,
morning and evening to attain spiritual enlightenment, mental
9
peace, purification of the mind and environment. From time im-
memorial, human beings have used smoke of medicinal plants for
curing disorders. Smoke produced from natural substances has been
used extensively in many cultures and famous ancient physicians
have described and recommended such use. Under the Saraswati-
Indus civilization 7500 BC,10 the great Rishis (saints) used to perform
agnihotra-yagnas to purify the environment as described in
Rigveda-the most ancient compilation of knowledge on earth by sub-
limating the Hawan samagri (mixture of wood with odoriferous and
medicinal herbs) in the fire accompanied by the chanting of Vedic
11
mantras described in Rigveda. Smoke produced at high temper-
atures is considered as a simple way of administering a drug, which
exhibits rapid pharmacological activity when inhaled. The sublimated
vital elements and herbal medicines inhaled in Yagya first reach the

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/)
which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
34 Journal of Epilepsy Research Vol. 5, No. 2, 2015
brain, followed by lungs and other subtle components of the body.
Thus, it has a direct healing effect on brain born diseases and com-
plexities. Ayurveda also recommended nasal route as a preferred
12
mode of administration of drugs for epilepsy. In addition to it, an-
cient scholars also recommended the patients to hold Hawans in a
frequently managed manner but the people used to follow just be-
cause of superstitions. So the present manuscript is designed to high-
light the scientific evidences that support possible prevention/cure of
epilepsy through Hawan. The present manuscript is intended to high-
light and integrate the modern and ancient concepts for treatment
and prevention of epilepsy.
Biochemical/molecular view of epilepsy
Epileptic seizures caused by imbalance between excitatory and in-
hibitory processes in the brain are due to abnormalities in the mem-
brane properties of neurons, changes in the ionic micro environment
surrounding the neuron, decreased inhibition of neurotransmission
(by gamma-amino butyric acid, GABA) or enhanced excitatory neuro-
transmission by the acidic amino acid glutamate. All ionotropic gluta-
+ +
mate receptors are permeable to Na and K and it is the influx of
+ +
Na and outflow of K through these channels that contribute to
membrane depolarization and generation of the action potential. The
++
n-methyl d-aspartate (NMDA) receptors also has a Ca channel that
++
is blocked by Mg ions in the resting state, but under conditions of
++
local membrane depolarization, Mg is displaced and channel be-
++ ++
comes permeable to Ca ions. Influx of Ca tends to further depo-
++
larize the cell, and is also thought to contribute to Ca mediated
neuronal injury under conditions of excessive neuronal activation
(e.g. status epilepticus) potentially leading to cell death, a process
13,14
termed excitotoxicity.
In epilepsy, when the number of free radicals in the brain neurons
increases, this interferes with respiratory chain in the mitochondria,
destabilizes the lysosomal membranes, and lowers the convulsion
15-17
threshold. Neuronal firing may lead to a number of neuro-
chemical changes and cascades of events at the cellular and molec-
ular level like mitochondrial dysfunction, increased ROS and nitric ox-
ide (NO) which precedes neuronal degeneration and death with pos-
sible subsequent epileptogenesis. Experimental data indicate in-
volvement of NO in pathophysiology of epileptic seizures by decreas-
ing synaptosomal GABA up-take and reduced availability of GABA at
the synapses leading to an increase of neuronal firing. Mitochondria
are emerging as key participants in cell death because their associa-
18
tion with an over-growing list of apoptosis-related problems.
Copyright ⓒ 2015 Korean Epilepsy Society
Peroxidation of neuronal membranes modifies their electrophysio-
logical properties and leads to abnormal bioelectric discharges of
neurons. Among diseases involving dysfunction in the mitochondrial
structures, epilepsy is prominent. Mitochondria have important vital
functions such as energy production, cellular harm control, neuro-
transmitter synthesis and free radical production however, it is still
19
not clear which of these functions is affected in epileptic seizures. It
is interesting to note that oxygen stress and mitochondrial dysfunc-
17,20
tion may both cause and be caused by epileptic attacks. Now a
day work is focused on the possible interaction between oxidative
stress resulting in disturbance of physiological signaling roles of cal-
cium and free radicals in neurons, mitochondrial dysfunction, cell
21
damage and epilepsy. Role of oxygen stress has been well demon-
strated and discussed in experimental animal model of epileptic
19, 22, 23
seizures.
Mechanism of action of present drug module for
epilepsy
The objective of the therapeutic management of seizures with
medication is to control the seizures with minimal adverse side
effects. Although the actions of each AED have unique characteristics
and some drugs may act by multiple mechanisms, the anti-seizure ac-
tions of these drugs can be grouped into four broad categories like,
modulation of voltage-dependent sodium, calcium or potassium
channels; increase in GABA-ergic inhibition via actions on GABAA re-
ceptors or on GABA synthesis, reuptake, or degradation, decreased
synaptic excitation via actions on ionotropic glutamate receptors;
modulation of neurotransmitter release via presynaptic mechanisms.
The drugs presently available for epilepsy are having renowned side
effects like tolerance, dependence, and long term defects like psy-
chosis, osteoporosis etc.
What is Hawan
Hawan is a Sanskrit word which refers to any ritual that involves
making offerings into a consecrated fire. It was done by ‘Rishis ’ in
early period and is an important religious practice in Hinduism where
they are part of most Sanskar ceremonies. They are also prevalent in
current-day Buddhism and Jainism. A consecrated fire is the central
element of every Hawan ritual however the procedure and items of-
fered to the fire vary by occasions/ceremony or by the benefit ex-
pected from the ritual. A Hawan (homam, yagya or agnihotra) is a sci-
entific experiment in which special herbal/plant medicinal prepara-
tions (Hawan Samagri ) are offered in the fire of medicinal woods ig-
 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 35
nited in a specially designed inverted pyramid shaped fire pit or con-
tainer (called agni-kuñda). The specific shape and size of the ag-
ni-kuñda, the arrangement of wood pieces in it, the time-frequency
and amount of Hawan Samagri account for controlled chemical proc-
essing in the fire and lead to sublimation, chemical conversion and/or
transformation into vapor phase of the herbal/plant medicinal prepa-
24-27
ration leading to release of medicinal phytochemicals. The de-
composition and transformation (into vapor or gaseous phase/colloi-
dal forms, etc) of specific substances in the yagya -fire is a scientific
method of subtlization of matter into energy and expanding its po-
tential and positive effects. The electromagnetic waves generated
thereby compounded with the sonic signals encoded in the mantras
help in intensifying and transmitting the desired benefits of yagya in
24,26
the surroundings atmosphere and far beyond.
Hypothesis behind action of Hawan on epilepsy
A recent study in South Africa has been conducted on traditional
healers. These healers believed that epilepsy could be caused by
amafufunyana (evil spirits) and that biomedical doctors could not
treat the supernatural causes of epilepsy. However, the healers be-
lieved that western medicines as well as traditional medicines could
28
be effective in treating the epileptic seizures. In a recent study, it
was found that majority of subjects had belief that prayer or pooja or
Hawan can reduce the bad effects and ghost can be removed by tan-
triks/ojha for mental disorders. Although literacy level has improved
29
in India, yet there are many false beliefs about Epilepsy. The hy-
pothesis behind action of Hawan on epilepsy is integration of modern
and ancient concepts. As per modern science, it is a known fact that
nasal drug delivery systems are the best drug delivery systems for the
30
diseases related to brain.
It is to be noted here that the traditional systems of treatment of
physical diseases employ medicines that are mostly administered or-
ally and therefore, produce effects only after they have been digested
and absorbed into the system. Most part of the medicine taken orally
is not even utilized and absorbed by the digestive system. Such medi-
cines may upset digestion and can have serious side effects. The
same is more or less true when medicines are directly injected into
the blood through intravenous route. They produce quicker results,
but their adverse side effects are often more pronounced.
According to oldest ancient texts on medicine, Nasya hi shirsho
dwaram means nose is the best route for administration of the drugs
for the diseases related to brain and head. There are some disorders
that may require a constant concentration of medicine for curative
and prophylactic measure. For medication and direct delivery of
drugs to the brain, drugs need to pass blood brain barrier. Other pre-
requisite for brain delivery is the nano-form or vapor form of drug
that can be easily taken up through mucous membrane. These days
the formulations are being designed in such a way that drug delivery
is targeted and desired concentration of the drug is delivered at a tar-
get site where required drug concentration is needed.
The rapid intranasal delivery of therapeutic agents such as nerve
growth factor to mouse brain allowed the by-passing of the blood
brain barrier. The olfactory neural pathway provides both intra-neuro-
nal (via axonal transport a highly time consuming process) and ex-
tra-neuronal (via bulk flow transport through peri-neural channels
31
taking only few minutes) access to the brain. Traditional ar-
oma-therapeutic practices, dating back thousands of years, are thus
st
verified by 21 century neuroscience. Equally fascinating is the evi-
dence that an odor-enriched environment increases neurogenesis in
32
adult mouse brain. Since agents promoting neurogenesis in adult
human brain, including the hippocampus, are being investigated in a
variety of psychiatric disorders (e.g. depression, dementia and schizo-
33
phrenia). Thus aromatherapy may have long-term protective poten-
34
tial in terms of regeneration is fascinating. One novel method of
herbal delivery, called ‘Nasya’, involves intranasal delivery of dry
herbal powders or medicated oils and is a practical, non-invasive,
rapid, and simple method to deliver the therapeutic agents into the
35
central nervous system (CNS). There are number of advantages of
intranasal delivery as it bypasses the BBB, targets the CNS, reduces
systemic exposure and systemic side effects. Rich vasculature and
highly permeable structure of the nasal mucosa greatly enhance drug
absorption, minimizes the degradation problem of peptide drugs,
significantly increases accessibility to blood capillaries, and avoids
destruction in the gastrointestinal tract, hepatic “first pass” elimi-
nation and gut wall metabolism allowing increased bioavailability.
The process of yagya magnifies the advantages of the desirable
medicinal phytochemicals and other healthy nutritional substances.
Medicines and herbs are vaporized by offering them into the sacrifi-
cial fire and enter the human body in a gaseous form through the
nose, lungs and the pores of the skin. This might prove to be easiest,
least taxing, least risky and most effective method of administering a
medicine so as to reach every single cell of the body. Further, the
thermal and associated aerodynamic characteristics of the base-fire
cause the sublimated/ vaporized substances to traverse and diffuse
everywhere in the surroundings where yagya is being conducted.
Hawan seems to be designed by the ancient scholars to fight with
www.kes.or.kr
36 Journal of Epilepsy Research Vol. 5, No. 2, 2015
Figure 1. A diagrammatic representation of components of Hawan Samagri along with probable nultiple mechanism of action.
the diseases of the brain. The components of Hawan are having a
number of volatile oils that volatilize due to high temperature of fire.
The vapors of these oils enter into the central nervous system through
nasal route. The routine of performing Hawan might keep the thresh-
old value of the therapeutic components in the body and help in pre-
venting epilepsy (Fig. 1).The scientific studies conducted on various
components of Hawan clearly demonstrates that Hawan was de-
signed for multifaceted action to clean the environment as well as to
cleanse the body of the toxins responsible for causing diseases re-
35
lated to brain. Hawan fumes are not only used for the disinfection
of air but also it can be environmentally oppressed for the physical,
mental, intellectual and spiritual development based on nano-
27
technology of Hawan.
Scientific evidences for effect of Hawan on epilepsy
The purpose of Hawan is to enhance the energy of the human
body and make it healthy and progressive. The therapeutic value of
Hawan is based on the ingredients used (Table 1). One of the main
Copyright ⓒ 2015 Korean Epilepsy Society
ingredients used is cow “Ghee” or “Clarified Butter” which has enor-
mous beneficial properties. This ghee when burnt like oil will produce
natural fumes that heal the respiratory system and clear any blood
clots and bacterium affecting the nasal, lungs and veins. In the bible,
the Book of Samuels, Chapter 2, “the burning of sins, using the sticks
and clarified butter” infers that ghee was frequently used for fire rit-
uals in biblical times. Essential oil constituents that penetrate the na-
sal passages, skin or lungs have direct actions on the autonomic
nervous system that can be grouped as relaxing or stimulating in
terms of basic responses such as heart rate, blood pressure and respi-
36-42
ration, in addition to localized dermal and bronchial effects. The
direct neuro-pharmacological properties of an essential oil, aroma of
the oil may exert a pleasant response via the olfactory system in turn,
altering the hypothalamic control of hormones and neurotransmitters.
The medium chain fatty acids in pure Ghee get converted into ke-
tones and supply the epilepsy patient brain with the energy it needs
to survive and if given on a continual basis will support processes in
the brain that are involved in healing and repair.
 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 37

Table 1. Therapeutic mechanism of action and active constituents of different components of Hawan Samagri on epilepsy
S. Name/botanical
Active component Mechanism of action
No name
1. Saffron Crocetin, picrocrocin, safranal, isophorone, 2,2,6-trimethyl-1,4-cyclohexanedione, Increase in seizure threshold.
Crocus sativus 4-ketoisophorone, 2-hydroxy-4,4,6-trimethyl-2,5-cyclohexadien-1-one as well Block PTZ induced convulsions.
as 2,6,6-trimethyl-1,4-cyclohexadiene-1-carboxaldehyde Increase GABA-ergic neurotransmission.
46,47
Inhibit absence seizures.
Improve tonic clonic seizures.
2. Jatamansi Valeranone, Calerene, patchouol, α-gurjunene, aristolone, β-maaliene, Increase in seizure threshold,
55
Nardostachys spathulenol Inhibit the electroshock convulsions.
57
jatamansi Increase GABA, 5-HT, 5-HIAA.
3. Coconut Monounsaturated fatty acids, Saponins Inhibit PTZ induced convulsions.
76
Cocos nucifera Increase GABA level, serotonin level.
Anticonvulsant.78
80
4. Sesame seeds 1-(5-methyl-2-furanyl)-1-propanone, 3-formylthiophene, Decrease ROS, MDA in epileptics.
Sesamum 2-propyl-4-methylthiazole, 2-ethyl-4-methyl-1H-pyrrole,
indicum 2-ethyl-6-methylpyrazine, 2-ethyl-5-methylpyrazine, 4,5-dimethylisothiazole,
4,5-dimethylthiazole, 2,6-diethylpyrazine, 2-ethyl-2,5-dimethylpyrazine,
1-(2-pyridinyl) ethanone, and 1-(1-methyl-1H-pyrrol-2-yl) ethanone
5. Clove Eugenol, acetyl eugenol, β-caryophyllene, vanillin, crategolic acid, tannins, Increase onset of convulsions.
Eugenia gallotannic acid, methyl salycylate, flavonoids eugenin, kaempferol, Reduce duration of convulsions.
66
caryophyllus rhamnetil, eugenitin and triterpenoids like oleanolic acid. Delay onset on seizures.
Increase GABAergic and glycinergic
67,68
activity.
6. Nutmeg Myristicin and macelignan Inhibit seizures.
Myristica Reduce severity of seizures.58
fragrans
61
7. Nagkesar Sesquiterpene, diterpenes, triterpenes, carboxylic acids and saturated Reduce HLTE.
Mesua ferra hydrocarbons Inhibit MES induced convulsions.
Increase the onset time of seizures.
Decrease duration of seizure.
8. Tagar Valerian, valipotriates and GABA sesquiterpene, diterpenes, triterpenes, Sedative action.
Valeriana carboxylic acids and saturated hydrocarbons Decrease HLTE.
64
wallichi Anticonvulsant activity.
9. Agar Sesquiterpenes, benzylacetone, guaiene, anisylacetone and chromone Sedative action.62
Aquilana derivatives
malaccensis
10. Nagarmotha Cyperone, selinene, cyperene, cyperotundone, patchulenone, sugeonol, Anticonvulsant action.70,71
Cyperus kobusone and isokobusone, pinene (monoterpene) derivatives of
rotundus sesquiterpenes such as cyperol, isocyperol and cyperone.
11. Ber Flavonoids, saponins, tannins, vitamin A, vitamin B, sugars, mucilage, calcium, Anticonvulsant action.73
Zizphus jujuba phosphate & iron. The pulp contains moisture, protein, fat, carbohydrate,
calcium, phosphorus, iron, carotene, thiamine, riboflavin, vitamin C.
12. Phoolmakhane N-nornuciferine, O-nornuciferine, nuciferine, and roemerine, protein, amino Decrease tonic extensor convulsions.
72
Nelumbo acids, unsaturated fatty acids, minerals, starch, and tannins. Anticonvulsant action.
nucifera
13. Mango PGG, polyphenolics, flavonoids, triterpenoids, mangiferin, catechin, isomangiferin, Inhibit PTZ and MES induced convulsions.
Mangifera mangiferin, alanine, glycine, γ-aminobutyric acid, kinic acid, shikimic acid Increase GABA levels.
79
indica and the tetracyclic triterpenoids cycloart-24-en-3β, 26diol, 3-ketodammar-24 Anticonvulsant action.
(E )-en-20S, 26-diol, C-24 epimers of cycloart-25 en 3β,24,27-triol and
cycloartan-3β,24,27-triol.
PTZ, pentylenetetrazole induced; GABA, gamma-amino butyric acid; ROS, reactive oxygen species; MDA, malondialdehyde; MES, maximal
electroshock seizure; HLTE, hind limb tonic extension

Another important ingredient in Hawan is “Camphor” from the ritual, the body’s breathing system is cleared quickly and the person
plant Cinnamomum camphora. When the camphor is burnt in the fire will experience a “high” or elevated feeling during the ceremony.43

www.kes.or.kr
38 Journal of Epilepsy Research Vol. 5, No. 2, 2015
The use of CO2 as a cerebral stimulant to assist the patients suffer-
ing from lack of ventilation is common in medical world. Its use to
control and cure many mental disorders is also known to medical
science. Small amounts of CO2 inhaled by the persons performing
Yagna acts as a stimulant and more and more aromatic fumes are in-
44
haled which help in curing mental disorders.
Crocus sativus L. contains important constituents like crocetin, pic-
rocrocin, safranal that are main component for characteristic aroma.
Safranal is the aglycon of picrocrocin and are responsible for many
45
pharmacological actions. Saffron increased the seizure threshold,
the ability of saffron in to elevate seizure threshold and block penty-
lenetetrazole induced (PTZ) convulsions can be attributed to its mod-
ulatory effect on GABA neurotransmission. The probable mechanism
of anti epileptic activity has been shown to be by increasing the
GABAergic neurotransmission. They showed that acute admin-
istration of saffron showed protection against PTZ induced con-
vulsions. The animals showed only mild clonic convulsions followed
by recovery. This may be because of their interaction with GABA ben-
zodiazepine receptor complex. Another study also showed that pre-
treatment with saffron offered a significant protection both during
the development of PTZ induced kindling and also once kindling was
established. It may be due to blockade of GABAA-ergic mechanism
46,47
by both acute and chronic treatment of saffron. In another study,
ethanolic and aqueous extracts decreased the duration of tonic
48,49
seizures. Among the constituents of saffron extract crocetin is
mainly responsible for the above pharmacological activities. In tradi-
tional medicine, the stigmas of this plant have been used as an anti-
50
convulsant remedy. The aqueous and ethanolic extracts of C. sat-
ivus have shown anticonvulsant activity in PTZ and maximal electro-
shock seizure (MES)-induced seizures. Agents affecting the PTZ test
can inhibit absence seizures. The extracts have also been shown to
49
improve tonic clonic seizures. The mechanism (s) of anticonvulsant
activity of the extracts is not clear. Saffron has been reported to have
some behavioral effects on the central nervous system. In one study
an alcoholic extract of decreased the motor activity and prolonged
51
the sleeping time induced by hexobarbital. Another component of
saffron, crocin did not show any effect in pentylenetetrazole‐induced
52
convulsions in mice.
Jatamansi is a reputed Ayurvedic herb and used in various multiple
formulations. jatamansi has been used in the treatment of many dis-
ease and has several activities including anticonvulsant activity, anti-
parkinson’s activity, tranquillizing activity, hepatoprotective, neuro-
53 54
protective etc. Rao et al. have studied ethanol extract of the roots
Copyright ⓒ 2015 Korean Epilepsy Society
of N. jatamansi DC for its anticonvulsant activity and neurotoxicity,
alone and in combination with phenytoin in rats. The results demon-
strated a significant increase in the seizure threshold by root extract
against MES model as indicated by a decrease in the extension/flex-
ion ratio. Valeranone prolonged barbiturate anesthesia, impaired ro-
tarod performance, inhibited electroshock convulsions, and po-
55
tentiated the hypothermic effects. Limited results from behavioral
tests revealed that an extract from N. jatamansi exhibited significant
56
antidepressant activity. In another study the effect of acute and sub
chronic administration of alcoholic extract of the roots of N. jata-
mansi DC on nor epinephrine (NE), dopamine (DA), serotonin (5-HT),
5-hydroxyindoleacetic acid (5-HIAA), GABA, and taurine on male al-
bino Wistar rats was conducted. The acute oral administration of the
extract did not change the level of NE and DA but resulted in a sig-
nificant increase in the level of 5-HT and 5-HIAA. A significant in-
crease in the level of GABA and taurine was observed in the
drug-treated groups when compared to the controls. A 15-day treat-
ment resulted in a significant increase in the levels of NE, DA, 5-HT,
57
5-HIAA, and GABA.
Nutmeg (Myristica fragrans, MF) possesses anticonvulsant activity
against PTZ, MES and lithium-pilocarpine induced seizures and lower
doses were more effective in inhibiting seizures. The MF was without
any significant effect on picrotoxin-induced convulsions and motor
coordination but potentiated haloperidol induced catalepsy sig-
nificantly. MF indicated signs of both CNS depression as well as
stimulation. In various animal models of seizures used in study, the
anticonvulsant activity of MF decreased with increasing doses. In sta-
tus epilepticus, the animals receiving MF in a dose of 10 mg/kg re-
duced the severity of seizures at much earlier time. These observations
support the biphasic effect of MF on the central nervous system. MF
was without any effect on the duration of pentobarbitone- induced
sleep. Though the MES test predicts activity against generalized ton-
ic-clonic and cortical focal seizures and the PTZ test against absence
seizures, the underlying neuronal abnormality is poorly understood.
Diminution of brain GABA level has been reported after sub-con-
58
vulsive dose of PTZ. Picrotoxin, the antagonist of GABA at the post-
synaptic receptors, induced seizures in all the animals and its effect
was not antagonized even at the dose of 100 mg/kg suggesting that
59,60
GABA may not be involved in the anticonvulsant activity of MF.
Nagkeshwar (Mesua ferra) is also a component of Hawan samagri.
The ethanolic extract of M. ferrea flowers have been reported to re-
duce the duration of Hind limb tonic extension in a dose dependent
manner against MES model and inhibited MES-induced convulsions.
 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 39
Data also showed that M. ferrea flowers significantly increased the
onset time and decreased the duration of seizures by electroconvulsive
61
shock. Agarwood smoke functions as endocrine disruptor and Agar
62
wood have sedative property. Tagar wood Valeriana wallichii is an
important component of Hawan reported to contain valepotriates
and valerinic acids (with putative pharmacological activities). Root
hydroethanolic extract have shown a dose dependant reduction of
hind limb tonic extensor phase indicating potential antiepileptic ef-
fect on grand mal type of epilepsy in man. The extract didn’t show
63
any adverse effects on motor coordination. Wood extract used for
64
its sedative action and anticonvulsant activity have CNS depressant
65
action and also have anti-convulsant effect.
Clove is also an important part of Hawan Samagri. Clove essential
oil (CEO) has been shown to significantly increase the onset of con-
vulsion and reduce its duration in dose dependent manner compared
to the control for strychnine and picrotoxin-induced convulsion. The
study indicates anticonvulsant, anxiolytic and hypnotic activity of
CEO. The anticonvulsant activity of a novel compound is not meas-
ured only by its ability to prevent convulsions but also to delay the
66
onset of seizures or to reduce death rate. These observations also
suggest that the CEO has considerable glycinergic and GABA-ergic
potentiating mechanisms. Glycine and GABA are amino acids, which
act as inhibitory neurotransmitters in the central nervous system and
their inhibition has been implicated in convulsions. Strychnine, a po-
tent spinal cord convulsant, blocks glycine receptors selectively to in-
duce excitatory response in the central nervous system. Picrotoxin,
on the other hand, blocks GABAA receptors to induce generalized
67
seizures. The anticonvulsant action of the CEO was probably due to
inhibition of the effects of strychnine and picrotoxin at glycine and
GABAA receptor sites respectively. CEO has also been shown to act
68
against neurotoxic death usually caused by chemical convulsants.
69
Nagaramotha (Cyperus rotundus) is an important herb in the Ayurveda.
Cyperotundone and α-cyperone compounds have been reported
from essential oil of C. rotundus rhizomes. The effect of Cyperus es-
culentus and Cyperus rotundus essential oils has been reported as
anticonvulsant (MES produced convulsion). The results showed dose
dependent activity in the maximal electroshock (MES) induced con-
70
vulsion in comparison to Diclofenac sodium. Nagarmotha is also
71
known to have Iso curcumenol used as sedative. Nelumbo nucifera
72
have reduced the tonic extensor convulsion induced by MES. The
wood of Zizphus jujube is used in Hawan and the hydro-alcoholic ex-
tract of z. jujuba demonstrate the anticonvulsant effect as well as
73
amelioration of cognitive impairment induced by seizures in rats.
The ethanol extract of Cocos nucifera was tested for possible phar-
macological effects on experimental animals. Pretreatment with ex-
tract caused significant protection against PTZ induced convulsions.
The behavioral studies on mice indicate CNS depressant activity of
the ethanol extract of C. nucifera. EECN potentiated significantly the
duration of pentobarbital, diazepam and meprobamate induced
sleep in mice, suggesting probable tranquilizing action as well as
74,75
CNS depressant action. It was found to increase the brain seroto-
nin and GABA level in mice (unpublished data). Therefore, profound
analgesic and anticonvulsant activities produced by extracts may be
76
related to the increased brain serotonin and GABA level in mice.
The mechanism whereby extract depressed awareness, touch and
pain responses, righting reflex, pinna reflex, corneal reflex, and grip
strength may also be due to synapse block of the efferent pathway or
77
by overall CNS depressant action. The exact chemical components
responsible for such CNS depressant activity of extract are not known.
Preliminary phytochemical studies revealed that it contains saponin
78
which might be responsible for anticonvulsant properties of extract.
The extracts also enhanced sleeping time, analgesic, and anti-
convulsant activities and reduced different behavioral reflexes. In a
study 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG) isolated
from methanolic leaf extracts of Mangifera indica showed significant
and dose-dependent inhibition of PTZ and MES-induced convulsions.
Furthermore, PGG administration showed significant decrease in the
locomotor activity as an indication of its CNS-depressant property;
also, PGG has significantly increased the GABA levels in the cer-
ebellum and whole brain other than the cerebellum. In conclusion,
PGG isolated from M. indica showed potent anticonvulsant activity,
and possible mechanism may be due to enhanced GABA levels in the
79
brain.
The pathogenesis of epilepsy has been strongly affected free radi-
cals and authors have tried to hypothesize antioxidant action (Table
2) of each component of Hawan Samagri. Components of Hawan like
Guggal, Saffron, Almond, Jatmansi and Coconut scavenge free radi-
cals and hence might be helpful to stop the pathogenesis of the
disease. Sesamum indicum, Sesamin is a well-known antioxidant
from sesame seeds and it scavenges free radicals and significantly
80
decreased ROS.
Nitric Oxide is an important neurotransmitter and also related to
synaptic plasticity, neuronal excitability regulation, and epileptic
81
activity. NMDA glutamate receptors activate calcium release via
NMDA receptor that consequently activates calcium calmoduline
pathway to increase neuronal nitric oxide synthase protein expression
www.kes.or.kr
40 Journal of Epilepsy Research Vol. 5, No. 2, 2015

Table 2. Components of Hawan Samagri along with probable multiple mechanism of action
S. No Name/botanical name GABA/serotonin/5-HIAA Antioxidant activity Nitric oxide level NMDA
1. Saffron (Crocus sativus) × × × ×
2. Jatamansi (Nardostachys jatamansi ) × × ×
3. Coconut (Cocos nucifera) × ×
4. Sesame seeds (Sesamum indicum) ×
5. Clove (Eugenia caryophyllus) × × ×
6. Nutmeg (Myristica fragrans) ×
7. Nagkesar (Mesua ferra) ×
8. Tagar (Valeriana wallichii ) × ×
9. Agar (Aquilana malaccensis)
10. Nagarmotha (Cyperus rotundus) × × ×
11. Ber (Zizphus jujube) ×
12. Phoolmakhane (Nelumbo nucifera) ×
13. Mango (Mangifera indica) ×
14. Ghee
15. Camphor laurel (Cinnamomum camphora)
16. Guggal (Commiphora weightii ) × ×
17. Almond (Prunus amygdalus) ×
18. Gular (Ficus racemosa) ×
19. Chirongi (Bauchanania lanzan)
20. Kapurkachri (Hedychium spicatum)
21. Red sandal (Pterocarpus santalinus)
NMDA, n-methyl d-aspartate

and NO increment in brain different area. The higher NO level is able
to increase the induction of generalized epilepsy. NO is known as a
molecule that can easily react with O2- radicals in the brain and re-
duce the oxidative stress induced damage via deleting free radicals.82
It has been reported in a study that Hawan causes a reduction in
NO levels in the atmosphere.83 The reduction in level of NO may be
helpful in reducing the epileptic seizures. Other components of
Hawan samagri have also been reported to reduce NO levels through
various mechanisms (Table 2). Methanol extracts of Nardostachys ja-
tamansi have been shown to exert inhibitory effect on nitric oxide
(NO) production. The NO level decreased from 100% to 5.8% and
this decreased levels could prove to have antiepileptic effect. NJ ex-
tracts down regulated iNOS in a dose-dependent manner.84 In anoth-
er study saffron extract has been related to a decrease in the NO
concentration.85 Lotus seed extract have been shown to possess free
radical scavenging properties.86,87 Results showed that all the ex-
tracts inhibit nitric oxide accumulation and thus could be helpful in
antiepileptic action. Results of a study showed that clove oil and its
major constituent, eugenol, were the most active inhibitors of the ni-
tric oxide production.88 C. rotundus rhizomes ethanolic exhibits its
scavenging effect in concentration dependent manner on superoxide
anion radicals, hydroxyl radicals, nitric oxide radical, hydrogen per-
oxide and it had a property of metal chelating and reducing power.
This antioxidant activity could be helpful in preventing epilepsy.89 The
methanol and EtOAc fraction of C. wightii has been shown to inhibit
the NO formation by down regulation of iNOS and COX-2 gene
expression.90 Guggulipid prevented the production of NO and ROS
generation91 in rat astrocytoma cell line. Nishaa et al.92 and K.
Kamalakara et al.93 have reported nitric oxide scavenging activity of
M. ferrea pet ether and methanol extract. The biflavone and tannin
fraction form Ficus racemosa bark extract has shown inhibitory action
on nitric oxide and hydroxyl radicals in in-vitro studies.94 Cyperus ro-
tundus extract suppressed the production of NO and the inhibition of
NO production by the extract was due to the suppression of iNOS
protein, as well as iNOS mRNA expression, determined by Western
and Northern blotting analyses, respectively.95
Also, other constituents of C. rotundus including sugeonol and cy-
perone, could yield a modulatory effect on glutaminergic system, es-
pecially lowering the opening of NMDA receptor channels,96 which
could lead to anticonvulsant effects. Ziziphus jujube (SZS) has been

Copyright ⓒ 2015 Korean Epilepsy Society

 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 41
97-100
shown to have sedative, analgesic and antiseizure effects.
2+
NMDA-induced intracellular Ca increase was almost completely
101
abolished by SZS a qualitatively stronger effect than other herbs
2+
that only partially diminished the Ca response. The subsequent
ROS production and cell death was also reduced by SZS. Similar to RP,
SZS also suppresses glutamate release and may suggest additional
101
protection for excitotoxicity. Ethanol extract of Valeriana abolished
102
cell death in NMDA-stimulated mouse cortical neurons. In the
same study, kainate-induced cell death was marginally decreased
only, suggesting the selective effect of extract on NMDA-R over other
102
glutamate receptor subtypes. An inhibitory effect on glutamate
binding of NMDA-R was only observed when isoborneol was present
103
at a high concentration. It is therefore likely that the NMDA-R-se-
lective cellular effects reported by Jacobo-Herrera et al. were attrib-
uted to a high concentration of isoborneol or other extract con-
102
stituents yet to be identified in the ethanol extract. Moreover, the
use of whole extract in targeting NMDA-R activity is cautioned due to
the multi-faceted effect on all glutamate receptor subtypes, iono-
tropic and metabotropic. Evidence of the inhibition of post-
synaptically located NMDA and kainite receptors by a hydro-etha-
nolic Crocus sativus L extract have been reported, which is partly
mediated by trans-cocetin. These mechanisms contribute to the neu-
104
roprotective effect of saffron. Saffron has turned out to be the an-
105
tagonist of postsynaptic NMDA receptors. Several studies have
demonstrated that oxygen free radicals formed by xanthine/xanthine
oxidase (X/XO) may be involved in the NMDA-mediated neurotoxicity
106-108
and inhibitory action of glutamate uptake in glial cells. The re-
sults of another study showed that eugenol attenuated NMDA in-
duced acute neurotoxicity and inhibited NMDA- induced elevation in
2+
neuronal Ca uptake. Furthermore eugenol prevented acute neuro-
nal swelling and reduced neuronal death and significantly reduced
109
oxidative neuronal injury induced by X/XO. Eugenol increased the
degree of INa activation and reversibly suppressed non-activating INa.
+2
In addition, at higher concentrations eugenol diminished L-type Ca
current and delayed rectifier K+ current. In pilocarpine-induced seiz-
ures in rats, a lower seizure severity and mortality was noted, though
no shorter seizure latency effect was observed. The mechanism of ac-
tion was deduced to be the synergistic blocking of INa and non-acti-
110
vating INa affecting neuronal spontaneous action potentials.
Mangifera indica L. extract attenuates glutamate-induced neuro-
toxicity on neurons.
111
Apart from the significant physical and medical applications like
cleansing of the environment, curing bodily ailments and augment-
ing vitality and physical potentials, yagyopathy is also found to be of
immense use in treatment of psychosomatic disorders and psycho-
logical and psychiatric problems. The sublimated vital elements and
herbal medicines inhaled in Yagya first reach the brain and then to
the lungs and other parts, the gross as well as the subtle components
of the body. Thus, it has a direct healing effect on brain diseases and
complexities. The body absorbs the heat of its sacrificial fire and in-
hales the vapors of sublimated herbs through the skin-pores and
respiration. This elevated level of antioxidants upon reaching the
brain and the nerves eliminates the major cause of mental tensions.
The specific energy currents reduced by yagyagni and mantra shakti
have significant remedial effect on the disorders and diseases rang-
ing from headache, migraine, cold to mental dullness, intellectual de-
ficiencies, depression, insomnia, intemperance, epilepsy, schizo-
112
phrenia and varieties of manias.
Conclusions
From the metadata analysis it seems that Hawan has been de-
signed by the ancient scholars to fight with a plethora of diseases re-
lated to brain. As explained in text, more than 70% of the compo-
nents of Hawan samagri are having a number of volatile oils that vol-
atilize due to high temperature of fire. Most of the components have
been found to be having anticonvulsant activity through one or the
other mechanism. The action of maximum number of herbs is benzo-
diazepines, Phenobarbital, valproate like action that enhances
GABA-ergic inhibition. It is quiet likely that the other volatile compo-
nents those have not been explored for anticonvulsant action could
add to further therapeutic antiepileptic action. The components of
Hawan seem to have a multiple action in preventing epilepsy through
scavenging of free radicals, increase in level of antioxidants, decrease
in level of nitric oxide and other underlying mechanisms. From the
pharmacological potentials of the components it can be concluded
that the routine of performing Hawan might keep the threshold value
of the antiepileptic elements in the body and help in preventing epi-
lepsy however concerted efforts are required to prove the hypothesis.
References
1. Roy MK, Das D. Indian Guidelines on Epilepsy. Chapter 116. Section
16: Neurology Medicine Update 2013. The Association of Physician of
India. Retrieved from: http://www.apiindia.org/medicine_update_2013/
chap116.pdf (Accessed August 2014).
www.kes.or.kr
42 Journal of Epilepsy Research Vol. 5, No. 2, 2015
2. Kounteya S. Around 95% of Indian with epilepsy don’t get treatment
study. The Times of India. Retrieved from: http://timesofindia.indiatimes.
com/india/Around-95-of-Indians-with-epilepsy-dont-get-treatment-Study
/articleshow/16585514.cms (Accessed August 2014).
3. Andlin-Sobocki P, Jonss B, Wittchen HU, Olesen J. Cost of disorders of
the brainin Europe. Eur J Neurol 2005;12:1-27.
4. Majkowski J, Majkowska-Zwolińska B. Direct and Indirect Annual Costs
of Patients with Epilepsy in Poland-Prospective Multicenter Study.
Epileptologia 2010;18:141-52.
5. Leonardi M, Ustrun TB. The global burden of epilepsy. Epilepsia 2002;
43:21-5.
6. Brodtkorb E, Nakken KO. The relationship between epilepsy and reli-
giosity illustrated by the story of the visionary mystic Wise-Knut.
Epilepsy & Behavior 2015;46:99-102.
7. Giovagnoli AR, Meneses RF, Da Silva AM. The contribution of spiritu-
ality to quality of life in focal epilepsy. Epilepsy & Behavior 2006;9:
133-9.
8. Işler A, Turan FD, Gozum S, Oncel S. Complementary and alternative
approaches used by parents of children with epilepsy on epilepsy
management. Epilepsy & Behavior 2014;32:156-161.
9. Tewary R, Mishra JK. Hawan. An effective method to reduce fungal load
at small work places. Aerobiologia 1997;13:135-8.
10. Nigam R, Hashimi NH. Has sea level fluctuations modulated human
settlements in gulf of Khambat (Cambay)? Journal of Geological Society
of India 2002;59:583-4.
11. Kalyanraman S. Mleccha. Indus script and sarasvati hieroglyphs. Ban-
galore: Baba Saheb (Umakanta Keshava) Apte Smarak Samiti; 2004.
12. Jain S, Tandon PN. Ayurvedic medicine and Indian literature on epi-
lepsy Neurology Asia 2004;9:57-58.
13. Fischer JH, The epilepsy counseling guide. New Jersey: MPE Communi-
cations Inc; 1994.
14. Garnett WR. Epilepsy. Stamford, CT: Appleton and Lange; 1997, p.
1179-210.
15. Frantseva MV, Perez Velazquez JL, Tsoraklidis G, et al. Oxidative stress
is involved in seizure-induced neurodegeneration in the kindling mod-
el of epilepsy. Neuroscience 2000;97:431-3.
16. Frantseva MV, Perez Velazquez JL, Carlen PL. Changes in membrane
and synaptic properties of thalamocortical circuitry caused by hydro-
gen peroxide. J. Neurophysiol 1998;80:1317-26.
17. Waldbaum S, Patel M. Mitochondrial dysfunction and oxidative stress:
a contributing link to acquired epilepsy? J. Bioenerg. Biomembr 2010;
42:449-55.
18. Chang JC, Kou SJ, Lin WT, Liu CS. Regulatory role of mitochondria in
oxidative stress and atherosclerosis. World J. Cardiol 2010;2:150-9.
19. Rowley S, Patel M. Mitochondrial involvement and oxidative stress in
temporal lobe epilepsy. Free Radic. Biol. Med 2013;62:121-31.
20. Sullivan PG, Springer JE, Hall ED, Scheff S. Mitochondrial uncoupling
as a therapeutic target following neuronal injury. J. Bioenerg. Biomembr
2004;36:353-6.
Copyright ⓒ 2015 Korean Epilepsy Society
21. Martinc B, Grabnar I, Vovk T. The role of reactive species in epilepto-
genesis and influence of antiepileptic drug therapy on oxidative stress.
Curr. Neuropharmacol. 2012;10:328-43.
22. Majkowski J. Epileptogenesis-The role of oxygen stress. Epileptologia
2007;1:225-40.
23. Ryan K, Backos DS, Reigan P, Patel M. Post-translational oxidative
modification and inactivation of mitochondrial complex I in epilepto-
genesis. J. Neurosci 2012;32:11250-8.
24. Pathirana W, Abhayawardhana P, Kariyawasam H, Ratnasooriya WD.
Transcranial Route of Brain Targeted Delivery of Methadone in Oil.
Indian J Pharm Sci 2009;71:264-9.
25. Scorer CA. Preclinical and clinical challenges in the development of
disease-modifying therapies for Alzheimer's disease. Drug Discov Today
2001;6:1207-19.
26. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet.
2006;368:387-403.
27. Tripathi KD. Essentials of medical pharmacology. New Delhi: JP Brothers
Medical Published; 2010.
28. Keikelame MJ, Swartz L. A thing full of stories’: Traditional healers’
explanations of epilepsy and perspectives on collaboration with bio-
medical health care in Cape Town. Transcultural Psychiatry, 2015, doi:
10.1177/1363461515571626.
29. Kishore J, Gupta A, Jiloha RC, Bantman P. Myth, beliefs and percep-
tions about mental disorders and health seeking behavior in Delhi,
India. Indain J Psychiatry 2011;53:324-9.
30. Turker S, Onur E, Ozer Y. Nasal route and drug delivery systems. Pharm
World Sci 2004;26:137-42.
31. Sugawara Y, Hara C, Aoki T, Sugimoto N, Masujima T. Odor distinctive-
ness between enantiomers of linalool: difference in perception and
responses elicited by sensory test and forehead surface potential wave
measurement. Chem Senses 2000;25:77-84.
32. Guedes DN, Silva DF, Barbosa-Filho JM, Medeiros IA. Muscarinic ago-
nist properties involved in the hypotensive and vasorelaxant responses
of rotundifolone in rats. Planta Med 2002;68:700-4.
33. Nagai M, Wada M, Usui N, Tanaka A, Hasebe Y. Pleasant odors at-
tenuate the blood pressure increase during rhythmic handgrip in humans.
Neuroscience Letters 2000;289:227-9.
34. Ballard CG, Gauthier S, Cummings JL et al. Management of agitation
and aggression associated with Alzheimer disease. Nat Rev Neurol
2009;5:245-55.
35. Turker S, Onur E, Ozer Y. Nasal route and drug delivery systems. Pharm
World Sci 2004;26:137-42.
36. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR,
Motamedi F et al. Protective effects of saffron extract and its active
constituent crocin against oxidative stress and spatial learning and
memory deficits induced by chronic stress in rats. Eur J Pharmacol
2011;667:222-9.
37. Reddy PM, Gobinath M, Rao KM, Venugopalaiah P, Reena N. A Review
on Importance of Herbal Drugs in Cosmetics. International Journal of
 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 43
Advances in Pharmacy and Nanotechnology 2011;1:121-39.
38. http://www.coconutresearchcenter.org.
39. Makhija IK, Sharma IP, Khamar D. Phytochemistry and Pharmacological
properties of Ficus religiosa: An overview. Annals of Biological Research
2010;1:171-80.
40. Borhade P, Tankar A, Joshi S, Khandelwal K. Pharmacological Review
on Ficus Racemosa Linn. IJPRBS 2012;1:51-66.
41. Neelakanth MJ, Bhat MR, Taranalli AD, Veeresh B. Effect of Buchanania
lanzan Seeds on Learning and Memory in Normal and Memory Deficit
Rats. Journal of Researchers in Pharmabiomedica 2012;22:33-8.
42. Sharma S, Sharma J, Kaur G. Therapeutic uses of Elettaria cardomum.
International Journal of Drug Formulation and Research 2011;2:102-8.
43. http://www.vedicastrologer.org/homam/chandi/chandi_homam_english.pdf.
44. Joshi RR. The Integrated Science of Yagna. http://literature.awgp.org/
magazine/Akhand-Jyoti-english/2003/Mar Apr/ScientificAspectsofYajna.
45. Katariya DC, Nerkar N, Gadiya RV, Abhyankar MM. Detailed Profile of
Crocus Sativus. International Journal of Pharma And Bio Sciences
2011;2:530-40.
46. Sunanda BPV, Rammohan B, Kumar A, Kudagi BL. The Effective Study
of Aqueous Extract of Crocus Sativus Linn in Chemical Induced
Convulsants in Rats. World Journal of Pharmacy And Pharmaceutical
Sciences 2014;3:1175-82.
47. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of
stigma and petals of saffron (Crocus sativus) and its components, sa-
franal and crocin in guinea pigs. Fitoterapia 2006;77:446-8.
48. Abe K, Saito H. Effects of saffron extract and its constituent crocin on
learning behavior and long- term potentiation. Phytother Res 2000;
14:149-152.
49. Vida JA, Foye WO, Lemke TL, Williams DA. Principles of Medicinal
Chemistry. London: Williams and Wilkins; 1995, p.163-79.
50. Zargari A. Medicinal Plants. Tehran: Tehran University Press; 1990, p.
574-8.
51. Zhang Y, Shoyama Y, Sugiura M, Saito H. Effect of Crocus sativus L.
on the ethanol-induced impairment of passive avoidance perform-
ances in mice. Biol Pharm Bull 1994;17:217-21.
52. Sheng L, Qian Z, Zheng S, Xi L. Mechanism of hypolipidemic effect of
crocin in rats: Crocin inhibits pancreatic lipase. Eur J Pharmacol 2006;
543:116‐222.
53. Bagchi A, Oshima Y, Hikino H. Neoligans and lignans of Nardostachys
Jatamansi roots. Planta Med 1991;57:96-97.
54. Rao VS, Rao A, Karanth KS. Anticonvulsant and neurotoxicity profile
of Nardostachys jatamansi in rats. J Ethanopharmacol 2005;102:351-6.
55. Rucker G, Tautges J, Wenzl H, Graf E. Isolation and pharmacological
active its of the sesquiterpene valeranone from Nardostachys jata-
mansi DC (in Germen). Arzneimittelforschung 1978;28:7-13.
56. Metkar B, Pal SC, Kasture S. Antiepressant activity of N. jatamansi
DC. Indian J Nat Prod 1999;15:10-3.
57. Prabhu V, Karanth KS, Rao A. Effects of Nardostachys jatamansi on
biogenic-amine and inhibitory amino-acids in the rat-brain. Planta
Med 1994;60:114-7.
58. Ha JH, Lee DU, Lee JT et al. 4- Hydroxybenzaldehyde from Gastrodia
elata as active in the anti-oxidation and GABAergic neuromodulation
of the rat brain. J Ethnopharmacol 2000;73:329-33.
59. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801
on the lithium-pilocarpine model of status epilepticus in rats. Exp
Neurol 1989;106:172-80.
60. Sherman WR, Honchar MP, Honsel LY. Detection of receptor linked
phosphoinositide metabolism in brain of lithium treated rats: In: Bleasdale
TE, Eichborg J, Hauser C, editors. Inositol and Phosphoinositides: Me-
tabolism and regulation. Clifton NJ: Humana Press; 1989, p.49-65.
61. Tiwari PK, Irchhaiya R, Jain SK. Evaluation of anticonvulsant activity
of Mesua ferrea Linn. ethanolic flower extract. Int. J. Pharm. Life Sci
2012;23:1507-9.
62. Miraghaee SS, Karmi I, Becker LA, Psychobiological Assessment of
Smoke of Agarwood (Aquilaria spp.) in Male Rats 2011;5:45-50.
63. Lovelyn J, Rejeesh EP, Rao SN. Anticonvulsant Activity of Hyrdroethanolic
Extract of Valeriana Wallichii Root on Maximal Electroshock Induced
Seizure Model in Swiss Albino Mice. International Journal of Universal
Pharmacy and Bio Sciences 2013;2:66-70.
64. Murali A, Sudha C, Madhavan V, Yoganarasimhan SN. Anticonvulsant
and sedative activity of tagara (Nymphoides macrospermum). Pharma-
ceutical Biology 2007;45:407-10.
65. Velmurugan V, Arunachalam G, Ravichandran V. Anticonvulsant Activity
of Methanolic Extract Anticonvulsant Activity of Methanolic Extract of
Prosopis Cineraria (Linn) Druce Stem Barks. International Journal of
Pharm Tech Research 2012;4:89-92.
66. Kendall DA, Fox DA, Enna, SJ. Anticonvulsant profile of gamma vinyl
GABA. Neuropharmacology 1981;20:4-10.
67. Nicoll RA. Introduction to the pharmacology of CNS drugs. San
Fransisco: McGraw-Hill Medical; 2007, p.333-46.
68. Karangwa C, Esters V, Tits M et al. Characterization of the neuro-
toxicity induced by extract of Magnistipula butayei (Chrystobalanaceae)
in rats: effects of a new natural convulsive agent. Toxicon 2007;49:
1109-19.
69. Lavanya K, Prasada RA, Chakravarthy, Mahendran B. A Review on
Biological and Chemical Properties of Cyperus Species. Research Journal
of Pharmaceutical, Biological and Chemical Sciences 2014;5:1142-55.
70. Biradar S, Kangralkar VA, Mandavkar Y, Thakur M, Chougule N. Anti-
inflammatory, antiarthritic, analgesic and anti-convulsant activity of
cyperus essential oils. Int J Pharm Pharm Sci 2010;2:112-5.
71. Singh N, Pandey BR, Verma P, Bhalla M, Gilca M. Phyto-pharmaco-
therapeutics of Cyperus rotundus Linn.(Moha): An overview. Indian
Journal of Natural Products and Resources 2012;3:467-76.
72. Joshi MK, Joshi HB, Joshi KT, Joshi UT. Anticonvulsant Activity of
Chloroform Extract of Nelumbo Nucifera. Int. J. of Pharm. Res. Develop
2010;3:84-90.
73. Pahuja M, Meha J, Reeta KH, Joshi S, Gupta YK. Hydroalcoholic ex-
tract of Zizphus jujube ameliorates seizures, oxidative stress, and cog-
www.kes.or.kr
44 Journal of Epilepsy Research Vol. 5, No. 2, 2015
nitive impairment in experimental models of epilepsy in rats. Epilepsy
&behavior 2011;21:356-63.
74. Pal D.K., Panda C., Sinhababu S., Dutta A., Bhattacharya S. Evaluation
of Psychopharmacological effect of petroleum ether extract of Cuscuta
reflexa Roxb. Stem in mice. Acta Pol Pharm Drug Res 2003;60;481-6.
75. Mazumder UK, Gupta M, Pal DK, Bhattacharya S. CNS activities of
the methanol extracts of Cuscuta reflexa Roxb. Stem and Corchorous
olitorius L. seed in mice. Malaysian J. Pharm 2005;2:190-198.
76. Pal DK, Sahoo M, Mishra AK. Analgesic and anticonvulsant effects of
saponin isolated from the stems of Opuntia vulgaris Mill in mice. Eur.
Bull. Drug Res 2005;13:91-97.
77. Pal DK, Dutta S, Sarkar A. Evaluation of antioxidant activity of the
roots of Cyperus rotundus L. Acta Pol. Pharm. Drug Res 2006;68:
256-8.
78. Pal DK, Balasaheeb NS, Khatun S, Bandyopadhyay PK. CNS activities
of the aqueous extract of Hydrilla verticillata in mice. Nal Prod Sci
2006;12:44-9.
79. Viswanatha GL, Mohan CG, Shylaja H, Yuvaraj HC, Sunil V. Anticon-
vulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated
from leaves of Mangifera indica. Naunyn Schmiedebergs Arch Pharmacol
2013;386:599-604.
80. Hsieh PF, Hou CW, Yao PW et al. Sesamin ameliorates oxidative
stress and mortality in kainic acid induced status epilepticus by in-
hibition of MAPK and COX-2 activation. J. Neuroinflammation 2011;
8: 57-66.
81. Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu RG. Nitric
oxide: an endogenous anticonvulsant substance. Neuroreport 1993;4:
444-6.
82. Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy.
Clin. Chem 2001;303:19-24.
83. Abhang P, Patil M, Moghe P. Beneficial Effects of Agnihotra on
Environment and Agriculture. International Journal of Agricultural Science
and Research 2015;5:111-20.
84. Chunmei L, Myeong-Hyeon W. Nardostachys jatamansi (D. Don) DC
prevents LPS-induced inflammation in RAW 264.7 macrophages by
preventing ROS production and down-regulating inflammatory gene
expression. Food Science and Biotechnology 2014;23:903-9.
85. Parizadeh MR, Gharib FG, Abbaspour AR, Afshar JT, Mobarhan MG.
Effects of aqueous saffron extract on nitric oxide production by two
human carcinoma cell lines: Hepatocellular carcinoma (HepG2) and
laryngeal carcinoma (Hep2). Avicenna J Phytomed 2011;1:43-50.
86. Sohn DH, Kim YC, Oh SH, Park EJ, Li X, Lee BH. Hepatoprotective
and free radical scavenging effects of Nelumbo nucifera. Phytomedicine
2003;10:165-9.
87. Yen GC, Duh PD, Su HJ, Yeha CT, Wu CH. Scavenging effects of lotus
seed extracts on reactive nitrogen species. Food Chemistry 2006;94:
596-602.
88. Perez-Roses R, Risco E, Vila R, Penalver P, Canigueral S. Inhibitory ac-
tivity of nine essential oils on nitric oxide production by humanleukocytes.
Copyright ⓒ 2015 Korean Epilepsy Society
Planta Med 2009;75:17-26.
89. Nagulendran KR, Velavan S, Mahesh R, Begum VH. In vitro antioxidant
activity and total polyphenolic content of Cyperus rotundus rhizomes.
J Chem 2007;4:440-9.
90. Cheng YW, Cheah KP, Lin CW et al. Myrrh mediates haem oxygen-
ase-1 expression to suppress the lipopolysaccharide-induced inflammatory
response in RAW 264.7 macrophages. J Pharmacy and Pharmacology
2011;63:1211-8.
91. Niranjan R, Kamat PK, Nath C, Shukla R. Evaluation of guggulipid
and nimesulide on production of inflammatory mediators and GFAP
expression in LPS stimulated rat astrocytoma, cell line (C6). Journal of
Ethnopharmacology 2010;127:625-30.
92. Nishaa S, Vishnupriya M, Sasikumar JM, Hephzibah PC, Gopalakrishnan
VK. Antioxidant Activity of Ethanolic Extract of Maranta Arundinacea
L Tuberous Rhizomes. Asian J Pharm Clin Res 2012;5:85-88.
93. Chaitanya KK, Rao KK, Sastry YN, Padal SB, Lakshmi AR, Rao DG.
Anti-inflammatory, antioxidant and phytochemical analysis of Mesua
ferrea bark extracts. IJCTPR 2015;3:891-902.
94. Nirmala S, Ahamed HN, Ravichandiran V. Comparative in vitro study
on the free radical scavenging capacity of tannin and biflavone frac-
tion from Ficus racemosa Linn and Araucaria bidwilli Hook. Interna-
tional Journal of ChemTech Research 2011;3:1440-5.
95. Won-Gil S, Hyun-Ock P, Gi-Su O et al. Inhibitory effects of methanol
extract of Cyperus rotundus rhizomes on nitric oxide and superoxide
productions by murine macrophage cell line, RAW 264.7 cells. Journal
of Ethnopharmacology 2001;76:59-64.
96. Ngo Bum E, Rakotoniria A, Rakotoniria SV, Herrling P. Effect of cype-
rus articulates compared to effects of anticonvulsant compounds on
the cortical wedge. Journal of Ethnopharmacol 2003;97:27-34.
97. Chen JK, Chen TT. Chinese Medical Herbology and Pharmacology.
City of Industry, USA: Art of Medicine Press; 2003, p.1031-74.
98. Yu-ching W. Handbook of Commonly Used Chinese Herbal Prescriptions.
Long Beach, USA: Oriental Healing Arts Institute; 1983, p.104-7.
99. Han BH, Park MH. Folk Medicine. Washington, USA: American Chemical
Society; 1986, p.205-9.
100. Huang KC. The Pharmacology of Chinese Herbs. Boca Raton, USA:
CRC Press; 1999, p.155-8.
101. Park JH, Lee HJ, Koh SB, Ban JY, Seong YH. Protection of NMDA-in-
duced neuronal cell damage by methanol extract of Zizyphi Spinosi
Semen in cultured rat cerebellar granule cells. J. Ethnopharmaol 2004;
95:39-45.
102. Jacobo-Herrera NJ, Vartiainen N, Bremner P, Gibbons S, Koistinaho J,
Heinrich M. NF-κB modulators from Valeriana officinalis. Phytother
Res 2006;20:917-9.
103. Del Valle-Mojica LM, Ayala-Marin YM, Ortiz-Sanchez CM, Torres-
Hernandez BA, Abdalla-Mukhaimer S, Ortiz JG. Selective interactions
of Valeriana officinalis extracts and valerenic acid with [3H] glutamate
binding to rat synaptic membranes. Evid. Based Complement. Alt.
Med 2011, 403591. doi: 10.1155/2011/403591.
 Parveen Bansal, et al. Epilepsy is a neuropsychiatric disorder associated 45
104. Nieber K, Berger F, Hensel A. Saffron extract and trans-crocetin in-
hibits excitotoxicity by inhibition of post-synaptically located gluta-
mate receptors in rat brain neurons, Proceedings of the British
Pharmacological Society. http://www.pA2online.org/abstracts/Vol10Issue
3abst006P.pdf.
105. Berger F, Hensel A, Nieber K. Saffron extract and trans-crocetin inhibit
glutamatergic synaptic transmission in rat cortical brain slices. Neuro-
science 2011;180:238-47.
106. Aizenman E, Hartnett KA, Reynolds IJ. Oxygen free radicals regulates
NMDA receptor function via a redox modulatory site. Neuron 1990;5:
841-6.
107. Volterra A, Trotti D, Racagni G. Glutamate uptake is inhibited by
arachidonic acid and oxygen radicals via two distinct and additive
mechanisms. Mol. Pharmacol 1994;46:986-92.
108. Volterra A, Trotti D, Tromba C, Floridi S, Racagni G. Glutamate uptake
inhibition by oxygen free radicals in rat cortical astrocyte. J. Neurosci
1994;14:2924-32.
109. Wie MB, Won MH, Lee KH et al. Eugenol protects neuronal cells from
excitotoxic and oxidative injury in primary cortical cultures. Neurosci.
Lett 1997;225:93-6.
110. Huang CW, Chow JC, Taid JJ, Wu SN. Characterizing the effects of
eugenol on neuronal ionic currents and hyperexcitability. Psychophar-
macology 2012;21:575-87.
111. Lemus-Molina Y, Sanchez-Gomez MV, Delgado-Hernandez R, Matute
C. Mangifera indica L. extract attenuates glutamate-induced neuro-
toxicity on rat cortical neurons. NeuroToxicology 2009;30:1053-8.
112. Heuberger E, Hongratanaworakit T, Bohm C, Weber R, Buchbauer G.
Effects of chiral fragrances on human autonomic nervous system pa-
rameters and self-evaluation. Chem Senses 2001;26:281-92.
www.kes.or.kr